Non-metastatic Castrate Resistant Prostate Cancer (nmCRPC)

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Metastatic hormone-sensitive Prostate Cancer (mHSPC)

Intended Audience: Oncologists, Urologists, Radiation Oncologists, Nuclear medicine, Community CPS, Nurses, Pharmacists, Patient/Caregivers

Bayer TA Rationale for Educational Support:

• Recent advancements in mHSPC, including biomarker‑ and imaging‑selected treatment approaches and emerging data on doublet and triplet systemic regimens, and how these developments should be integrated and positioned in clinical practice
• Evidence gaps and practical challenges in mHSPC clinical trials, particularly around recruitment, representativeness of enrolled populations, and the feasibility of addressing important clinical questions with traditional trial designs
• Understanding the role of novel and pragmatic trial designs in mHSPC, such as the use of historical or external comparators, artificial intelligence–enabled methods, and other pragmatic elements, to enhance efficiency, improve generalizability, and address difficult or infeasible clinical questions

Preferred Format:

• Enduring
• Downloadable slides
• Incorporation of social media outreach (You-Tube, FaceBook, Spotify, LinkedIn, Twitter)
• Podcast
• Live Virtual

Proposal Requirements:

The proposal must be compliant with standards and guidelines for commercial support (e.g., ACCME).

The proposal should include:

• Needs assessment
• Educational design and rationale for selection (where applicable)
• Learning Objectives
• Proposed Faculty
• Participant recruitment plan (where applicable)
• Outcomes strategy/plan
• Detailed budget (please use the template available on the website)

Provider Justification:

Copy of most recent accreditation letter and status

Process:

Applications/proposals which are submitted and determined to be complete are reviewed monthly. Allow a minimum of 45 days from submission for response.

Acceptance of a Bayer educational grant indicates that you will:

• Reconcile grant funding within 60 days of completion of the educational program
• Permit a Bayer Medical Affairs representative to audit live programs
• Share activity data and outcomes metrics within 30 days of their availability

Publication References

Treatment landscape in prostate cancer

1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer, Version 2.2021 – February 17, 2021. (Link)
2. American Cancer Society. Cancer Facts & Figures 2021. Atlanta; American Cancer Society. (Link)
3. Crawford ED, et al. Androgen Receptor-Targeted Treatments for Prostate Cancer: 35 Years' Progress with Antiandrogens. J Urol. 2018 Nov;200(5):956-966. (Link)
4. Morgans AK, et al. Androgen receptor inhibitor treatments: Cardiovascular adverse events and comorbidity considerations in patients with non-metastatic prostate cancer. Urol Oncol. 2021 Jan;39(1):52-62 (Link)
5. Spratt DE, et al. Treating the patient and not just the cancer: therapeutic burden in prostate cancer. Prostate Cancer Prostatic Dis. 2021 Feb 18. (Link)
6. Morgans AK, et al. Risk of Cognitive Effects in Comorbid Patients With Prostate Cancer Treated With Androgen Receptor Inhibitors. Clin Genitourin Cancer. 2021 Mar 18;S1558-7673(21)00077-X (Link) 
   nmCRPC disease state challenges and identification of appropriate patients 
7. Saad F, et al. Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors. Prostate Cancer Prostatic Dis. 2021 Jun;24(2):323-334. (Link)
8. Roumiguié M, et al. Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis. Future Oncol. 2021 May;17(14):1811-1823. (Link)
9. Fizazi K, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. (Link)
10. Shore, N et al. Evaluation of Clinically Relevant Drug–Drug Interactions and Population Pharmacokinetics of Darolutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Results of Pre-Specified and Post Hoc Analyses of the Phase III ARAMIS Trial. Targ Oncol (2019) 14: 527. (Link)
11. Sugawara T, et al. Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. Int J Cancer. 2019 Mar 3. (Link)
12. Sandmann S, et al. Higher Blood–Brain Barrier Penetration of [14C]Apalutamide and [14C]Enzalutamide Compared to [14C]Darolutamide in Rats Using Whole-Body Autoradiography. J Clin Oncol 37, 2019 (suppl 7S; 156). (Link)
13. Zurth, C., et al. Drug–Drug Interaction Potential of Darolutamide: In Vitro and Clinical Studies. Eur J Drug Metab Pharmacokinet. 2019 Sep 30. doi: 10.1007/s13318-019-00577-5. [Epub ahead of print] (Link)
14. Tammela TL, et al. Darolutamide elicits a strong prostate-specific antigen (PSA) response in men with non-metastatic castration-resistant prostate cancer (nmCRPC): Results from the ARAMIS study. European Urology 2018, in press. 
    
    Targeted Alpha Therapy
     
15. Sartor AO, et al. Lutetium-177-prostate-specific membrane antigen ligand following radium-223 treatment in men with bone-metastatic castration-resistant prostate cancer: real-world clinical experience. J Nucl Med. 2021 Jun 24 (Link)
16. Dizdarevic S. et al. Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice. Eur J Nucl Med Mol Imaging. 2019 May;46(5):1102-1110 (Link)
17. Sartor, AO et al. Re‐treatment with radium‐223: 2‐year follow‐up from an international, open‐label, phase 1/2 study in patients with castration‐resistant prostate cancer and bone metastases. Prostate. 2019 Oct;79(14):1683-1691. (Link)
18. Suominen, MI et al. The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis. Int J Mol Sci. 2019 Aug 10;20(16). pii: E3899 (Link)
19. Sartor AO., et al. A Retrospective analysis of Treatment Patterns in Metastatic Castration Resistant Prostate Cancer Patients Treated with Radium-223. J Clin Oncol 37, 2019 (suppl 7S, 180). (Link)
20. Smith M., et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):408-419 (Link)
21. De Vincentis G, et al. Advances in targeted alpha therapy for prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1728-1739 (Link)
22. Targeted Alpha Therapy Working Group, et al. Targeted Alpha Therapy, an Emerging Class of Cancer Agents: A Review. JAMA Oncol. 2018 Dec 1;4(12):1765-1772. (Link)
23. Louhanepessy RD, et al. Pain and quality of life in metastasized Castration Resistant Prostate Cancer patients treated with Radium-223 (ROTOR registry); a prospective observational registry in a non-study population. Ann. Onc., V29 (suppl_8, Oct 2018, 829P). (Link)
24. Sartor AO, et al. Chemotherapy following radium-223 dichloride treatment in ALSYMPCA. Prostate. 2016 Jul;76(10):905-16. (Link)
25. Saad F, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016 Sep;17(9):1306-16. (Link)
26. Maughan BL, et al. Safety data from a phase II randomized trial of radium-223 dichloride (Ra-223) plus enzalutamide (Enza) vs. Enza alone in men with metastatic castration refractory prostate cancer (mCRPC). J Clin Oncol 36, 2018 (suppl 15S; abstr 5057). (Link)
27. Parker C et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. (Link)
    
    Bone health
     
28. Gillessen S, et al. Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis. Eur Urol. 2019 Jun;75(6):894-895 (Link)
29. Tombal BF, et al. Decreased fracture rate by mandating bone-protecting agents in the EORTC 1333/PEACE III trial comparing enzalutamide and Ra223 versus enzalutamide alone: An interim safety analysis. J Clin Oncol 37, 2019 (suppl 15S; abstr 5007). (Link)
30. Den RB, et al. Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection. Am J Clin Oncol. 2019 Apr;42(4):399-406. (Link)
31. Poeppel TD, et al. Disease burden and bone health in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO non-interventional study. Eur Urol Suppl 2019; 18(1); e1210 (Link)
32. Tablazon IL et al. Predictors of skeletal-related events and mortality in men with metastatic, castration-resistant prostate cancer: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cancer. 2019 Nov 15;125(22):4003-4010 (Link)
33. Sternberg CN, et al. Use of Bone Health Agents in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Radium-223 After Abiraterone: an Interim Review of REASSURE. Ann. Onc., V29 (suppl_8, Oct 2018, 826P). (Link)
34. Volta AD, et al. Higher Risk of Fragility Fractures in Prostate Cancer Patients Treated with Combined Radium-223 and Abiraterone: Prednisone May Be the Culprit. Eur Urol. 2019 Jun;75(6):894-895 (Link)
35. Gralow JR, et al. NCCN Task Force Report: Bone Health in Cancer Care. JNCCN 2013, Vol 11, S 3 (Link) 
    
    Appropriate sequencing and combinations of agents in mCRPC  
     
36. George DS, et al. Clinical outcomes with concurrent or layered treatment with radium-223 and abiraterone plus prednisone/prednisolone: a retrospective study of real-world experience with patients with metastatic castration-resistant prostate cancer. J Clin Oncol 37, 2019 (suppl 7S, 253-253). (Link)
37. O’Sullivan, JM, et al. Radium-223 Within the Evolving Treatment Options for Metastatic Castration-resistant Prostate Cancer: Recommendations from a European Expert Working Group. European Urology 2018, in press. (Link)
38. Khalaf D, et al. Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI+P) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCPRC): Results for 2nd-line therapy. J Clin Oncol 36, 2018 (suppl; abstr 5015) (Link)
39. Matsubara N, et al. Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate Cancer. Clinical Genitourinary Cancer 2018, 16 (2), 142-148 (Link) 
    
    mHSPC/mCSPC?
     
40. McKay RR, et al. Darolutamide plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): ARASEC – U.S. prospective, open-label phase 2 study with an external control. Presented at: American Urological Association (AUA) Annual Meeting; 2026; Washington, DC.
41. McKay RR, Ross AE, Preston MA, Gregg JR, Salami SS, Littleton N, Constantinovici N, Srinivasan S, Verholen F, Shore ND. Darolutamide plus androgen-deprivation therapy: propensity score matching of ARASEC and historic clinical trial patients. Future Oncol. 2025 May;21(11):1365-1375. doi: 10.1080/14796694.2025.2482360. Epub 2025 Apr 1. PMID: 40165634; PMCID: PMC12051612.
42. Shore ND, McKay RR, Preston MA, et al. Time trends of overall survival and other outcomes in patients with mHSPC: an observational study of U.S. EHR data (TIMES). J Clin Oncol. 2022;40(16_suppl):e17051. doi: 10.1200/JCO.2022.40.28_suppl.403